Benjamin J Wheeler

Disorders of sex development: Insights from targeted gene sequencing of a large international patient cohort

BackgroundDisorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously.ResultsWe analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management.ConclusionsOur massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.

Effect of a Baby-Led Approach to Complementary Feeding on Infant Growth and Overweight: A Randomized Clinical Trial

Importance Baby-led approaches to complementary feeding, which promote self-feeding of all nonliquid foods are proposed to improve energy self-regulation and lower obesity risk. However, to date, no randomized clinical trials have studied this proposition. Objective To determine whether a baby-led approach to complementary feeding results in a lower body mass index (BMI) than traditional spoon-feeding. Design, Setting, and Participants The 2-year Baby-Led Introduction to Solids (BLISS) randomized clinical trial recruited 206 women (168 [81.6%] of European ancestry; 85 [41.3%] primiparous) in late pregnancy from December 19, 2012, through March 17, 2014, as part of a community intervention in Dunedin, New Zealand. Women were randomized to a control condition (n = 101) or the BLISS intervention (n = 105) after stratification for parity and education. All outcomes were collected by staff blinded to group randomization, and no participants withdrew because of an adverse event. Data were analyzed based on intention to treat. Interventions Mothers in the BLISS group received lactation consultant support (≥5 contacts) to extend exclusive breastfeeding and delay introduction of complementary foods until 6 months of age and 3 personalized face-to-face contacts (at 5.5, 7.0, and 9.0 months). Main Outcomes and Measures The primary outcome was BMI z score (at 12 and 24 months). Secondary outcomes included energy self-regulation and eating behaviors assessed with questionnaires at 6, 12, and 24 months and energy intake assessed with 3-day weighed diet records at 7, 12, and 24 months. Results Among the 206 participants (mean [SD] age, 31.3 [5.6] years), 166 were available for analysis at 24 months (retention, 80.5%). The mean (SD) BMI z score was not significantly different at 12 months (control group, 0.20 [0.89]; BLISS group, 0.44 [1.13]; adjusted difference, 0.21; 95% CI, −0.07 to 0.48) or at 24 months (control group, 0.24 [1.01]; BLISS group, 0.39 [1.04]; adjusted difference, 0.16; 95% CI, −0.13 to 0.45). At 24 months, 5 of 78 infants (6.4%) were overweight (BMI≥95th percentile) in the control group compared with 9 of 87 (10.3%) in the BLISS group (relative risk, 1.8; 95% CI, 0.6-5.7). Lower satiety responsiveness was observed in BLISS infants at 24 months (adjusted difference, −0.24; 95% CI, −0.41 to −0.07). Parents also reported less food fussiness (adjusted difference, −0.33; 95% CI, −0.51 to −0.14) and greater enjoyment of food (adjusted difference, 0.25; 95% CI, 0.07 to 0.43) at 12 months in BLISS infants. Estimated differences in energy intake were 55 kJ (95% CI, −284 to 395 kJ) at 12 months and 143 kJ (95% CI, −241 to 526 kJ) at 24 months. Conclusions and Relevance A baby-led approach to complementary feeding did not result in more appropriate BMI than traditional spoon-feeding, although children were reported to have less food fussiness. Further research should determine whether these findings apply to individuals using unmodified baby-led weaning. Trial Registration http://anzctr.org.au Identifier: ACTRN12612001133820

A Baby-Led Approach to Eating Solids and Risk of Choking.

OBJECTIVE: To determine the impact of a baby-led approach to complementary feeding on infant choking and gagging. METHODS: Randomized controlled trial in 206 healthy infants allocated to control (usual care) or Baby-Led Introduction to SolidS (BLISS; 8 contacts from antenatal to 9 months providing resources and support). BLISS is a form of baby-led weaning (ie, infants feed themselves all their food from the beginning of complementary feeding) modified to address concerns about choking risk. Frequencies of choking and gagging were collected by questionnaire (at 6, 7, 8, 9, 12 months) and daily calendar (at 6 and 8 months); 3-day weighed diet records measured exposure to foods posing a choking risk (at 7 and 12 months). RESULTS: A total of 35% of infants choked at least once between 6 and 8 months of age, and there were no significant group differences in the number of choking events at any time (all Ps > .20). BLISS infants gagged more frequently at 6 months (relative risk [RR] 1.56; 95% confidence interval [CI], 1.13–2.17), but less frequently at 8 months (RR 0.60; 95% CI, 0.42–0.87), than control infants. At 7 and 12 months, 52% and 94% of infants were offered food posing a choking risk during the 3-day record, with no significant differences between groups (7 months: RR 1.12; 95% CI, 0.79–1.59; 12 months: RR 0.94; 95% CI, 0.83–1.07). CONCLUSIONS: Infants following a baby-led approach to feeding that includes advice on minimizing choking risk do not appear more likely to choke than infants following more traditional feeding practices. However, the large number of children in both groups offered foods that pose a choking risk is concerning.

Incidence and characteristics of vitamin D deficiency rickets in New Zealand children: a New Zealand Paediatric Surveillance Unit study

Objective: To investigate the incidence and characteristics of vitamin D deficiency rickets in New Zealand (NZ).

Clinical review: the misreporting of logbook, download, and verbal self-measured blood glucose in adults and children with type I diabetes

Abstract Despite advances in technology, the frequent self-measurement of blood glucose (SMBG) remains fundamental to the management of 1 diabetes mellitus (T1DM). Once measured, SMBG results are routinely reported back to health professionals and other interested parties, either verbally, via a logbook, or electronically downloaded from a pump or meter. The misreporting of SMBG using various techniques represents a classic non-adherence behavior and carries with it both acute and chronic dangers. In addition, while this behavior appears very prevalent, many aspects remain largely unstudied. With this in mind, we aimed to summarize literature addressing the misreporting of SMBG in T1DM via a detailed literature search. This produced both recent and past literature. While most of these studies examined the prevalence of deliberate misreporting in a verbal or logbook context, others focused on the motivations behind this behavior, and alternative forms of misreporting, including deliberate manipulation of meters to produce inaccurate results and true technological errors. This timely review covers all aspects of misreporting and highlights multiple patient techniques, which are clearly adapting to advances in technology. We believe that further understanding and attention to this aspect of adherence may lead not only to improvements in glycemic control and safety, but also to the psychological well-being of those affected by type 1 diabetes.

Medical and midwifery attitudes towards vitamin K prophylaxis in New Zealand neonates.

Neonates are at risk for potentially life‐threatening vitamin K deficiency bleeding. This can be readily prevented with prophylactic vitamin K following delivery. In this context, most vitamin K‐deficiency bleeding occurs in those whose parents decline newborn vitamin K. One factor influencing parental decision‐making is information received from health professionals. This study examined attitudes and perceptions towards newborn vitamin K in relevant health‐care professionals.

Declining newborn intramuscular vitamin K prophylaxis predicts subsequent immunisation refusal: A retrospective cohort study

Low rates of childhood immunisation are linked to outbreaks of infectious disease. Identifying and addressing barriers to immunisation may lead to improved immunisation rates. Immunisation and newborn vitamin K prophylaxis have many similarities. We aimed to investigate whether parents who decline newborn vitamin K are also more likely to decline subsequent childhood immunisations.

Frequency and genetic spectrum of maturity-onset diabetes of the young (MODY) in southern New Zealand

Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes, consisting of a heterogeneous group of autosomal dominant inherited disorders. Typical onset is in individuals prior to twenty five years, and presentation can mimic type 1 or 2 diabetes. Molecular genetic testing can allow precise identification of the different MODY sub-types. Making a specific diagnosis of MODY can have important implications for the guidance of appropriate treatment, prognosis and genetic counselling.We present the cases of three children and their families diagnosed with MODY over the past two years. These families highlight the features of three of the more common MODY subtypes, including two with novel mutations, one of which segregates in a kindred that is strongly affected by both MODY and classic autoimmune mediated diabetes. To date, we have identified a prevalence of MODY in the paediatric diabetes population of the lower South Island, New Zealand, of approximately 2.5%. This prevalence, along with increasing access to molecular genetic testing, highlights the importance of consideration of MODY in atypical diabetes presentations in the paediatric/adolescent population.

After‐hours on‐call: The effect on paediatricians' spouses and families

The after‐hours or on‐call component of a paediatricians work has implications for their spouse and family. Little is known about the specifics and extent of this impact. We aimed to understand the potential positive and negative impacts of this important aspect of a paediatricians work.

Perinatal influences on the uptake of newborn Vitamin K prophylaxis – a retrospective cohort study

Objectives: To describe rates of newborn vitamin K prophylaxis uptake according to method of administration (intramuscular [IM], oral, refused) and identify predictors for the choice of oral administration and for refusal of vitamin K prophylaxis.